Antitumor Response of VEGFR2- and VEGFR3-Amplified Angiosarcoma to Pazopanib
Related Experiment Video
Updated: Mar 21, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Vinod Ravi1, Eric M Sanford2, Wei-Lien Wang1
1The University of Texas MD Anderson Cancer Center, Houston, Texas
Background:
Angiosarcoma is a malignant neoplastic disease originating from or differentiating toward vascular endothelium, for which systemic pharmacologic treatment has limited durability. The molecular oncogenesis of angiosarcoma is often linked to inappropriate activations of vascular endothelial growth factor receptor (VEGFR) family members, which presents an opportunity for the use of therapy that selectively targets the machinery of vascular signaling.
Methods:
Hybridization capture of 3,320 exons of 182 cancer-related genes and the introns of 14 genes frequently rearranged in cancer was applied to more than 50 ng of DNA extracted from a formalin-fixed, paraffin-embedded biopsy of recurrent angiosarcoma and was sequenced to high, uniform coverage of 939x.
Results:
The angiosarcoma harbored amplifications of VEGFR2 (KDR) of 8 copies and VEGFR3 (FLT4) of 16 copies. The patient was initially treated with sorafenib, an inhibitor of VEGFR2, and developed progressive disease. The patient then received pazopanib, an inhibitor of VEGFR2 and VEGFR3 and experienced a potent antitumor response resulting in clinically stable disease for 6 months.
Conclusions:
This exceptional response to pazopanib treatment suggests that a subset of patients with angiosarcoma with genomic alterations in vascular signaling genes may respond well to pazopanib.
Insights
Pazopanib shows promise for angiosarcoma patients with specific genetic alterations. This targeted therapy, inhibiting vascular endothelial growth factor receptors (VEGFRs), led to stable disease in a patient with VEGFR2 and VEGFR3 amplifications.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Angiosarcoma is a rare vascular cancer with limited treatment options.
- Its development is often driven by overactive vascular endothelial growth factor receptor (VEGFR) signaling pathways.
- Targeting these pathways offers a potential therapeutic strategy.
Observation:
- A patient with recurrent angiosarcoma underwent genetic sequencing of 182 cancer-related genes.
- The tumor showed significant amplifications of VEGFR2 (KDR) and VEGFR3 (FLT4).
Findings:
- Initial treatment with sorafenib (a VEGFR2 inhibitor) was ineffective.
- Subsequent treatment with pazopanib (a VEGFR2 and VEGFR3 inhibitor) resulted in a significant antitumor response and stable disease for six months.
Implications:
- Pazopanib may be an effective treatment for a subset of angiosarcoma patients.
- Genomic alterations in VEGFR family genes could predict response to pazopanib.
- This highlights the importance of targeted therapy in angiosarcoma treatment.
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